The present invention relates to inherently immunogenic constructs capable of eliciting an IgG, IgE or IgA antibody response in a host in the absence of adjuvant.
In an effort to prevent disease in a host caused by pathogens, the host body's immune system attempts to destroy the pathogen itself and neutralize its products. This strategy underlies the field of vaccination, which is based on two key elements of adaptive immunity: specificity and memory. Specificity increases a vaccine's effectiveness whereas memory cells allow the immune system to mount a stronger response in reaction to a second encounter with antigen. This secondary response is both faster to appear and more effective than the primary response.
The response to most antigens depends on both T cells and B cells recognizing that antigen. This type of antigen is called T-dependent. Antigen entering the body is processed by antigen presenting cells (APC) and presented to T helper cells. Antigen is recognized by B cells as well. The T cells deliver help to the these B cells which are consequently stimulated to differentiate and divide into antibody-forming cells.
A number of antigens are, however, capable of activating B cells without, or in the virtual absence of, T-cell help. These antigens are referred to as T-independent antigens. The immune response to T-dependent and T-independent antigens is qualitatively different. For example, the secondary response to T-independent antigens resembles the primary response. Such a secondary response to T-independent antigens usually does not exceed the primary response in magnitude and is almost entirely confined to IgM antibody production. In contrast, the secondary IgG antibody response to T-dependent antigens is far stronger and appears earlier. It seems therefore that T-independent antigens do not usually induce memory and maturation of the response as characterized by class switching to IgG antibodies and an increase in affinity of antibodies for antigen. Therefore, vaccines which do not elicit T cell help for B cells are of limited value.
In a response to a T-dependent antigen, it has been found that distinct sites on the antigen (epitope, hapten or antigenic determinant) are recognized by T and B cells, thus, these sites may be termed T-cell and B-cell epitopes, respectively. The vast majority of soluble T-dependent antigens elicit only low level antibody responses unless they are administered with an adjuvant, a substance which non-specifically enhances the immune response to an antigen. However, the use of adjuvants may be associated with several disadvantages: they are often toxic, they may skew the antibody repertoire to certain isotypes which may have different effector functions from those produced in the absence of adjuvants and they may alter the nature of the antigen so that epitopes other than those recognized in the native antigen become immunodominant. In addition, due to their size, many T-dependent antigens are non-immunogenic even in the presence of an adjuvant eg. synthetic peptides.
To overcome the disadvantages and to optimize the advantages of T-dependent antigens, various vaccines have been designed based on conjugates combining B and T cell epitopes. However, in many cases either low level production of antibodies was elicited, multiple immunizations were required, infants failed to mount a secondary response, or the conjugate required the presence of an adjuvant in order to elicit any response.
Therefore, a clear need exists for a vaccine capable of inducing the production of memory cells and of eliciting a specific immune response to pathogenic invaders.